Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of synthetic method of vildagliptin

A synthesis method and compound technology, applied in the field of pharmaceutical synthesis, can solve problems such as unfavorable environmental protection, increase product cost, high price, etc., and achieve the effects of less by-products, low cost, and improved reaction efficiency and conversion rate.

Active Publication Date: 2020-07-14
无锡科华生物科技有限公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Though this method yield and product quality improve to some extent, sodium metabisulfite used has strong SO smell, is unfavorable for environmental protection, and 2-picoline-N-borane price is more expensive, improves product cost

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of synthetic method of vildagliptin
  • A kind of synthetic method of vildagliptin
  • A kind of synthetic method of vildagliptin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Synthesis of Compound II

[0037] Glyoxylic acid monohydrate 27.6g (0.30mol, 1.5eq), 3-amino-1-adamantanol 33.5g (0.20mol, 1.0eq), diisopropylethylamine 38.8g (0.30mol, 1.5eq ) and 250g of tetrahydrofuran were put into the reaction flask, 51.1g (0.50mol, 2.5eq) of acetic anhydride was added dropwise, heated to reflux and stirred for 2 hours, the remaining raw materials were controlled in HPLC to be less than 1%, 50g of water was added, stirred for 30 minutes, and separated, The aqueous layer was extracted once with 50 g of dichloromethane, and the organic layer was concentrated under reduced pressure to obtain 42.8 g of off-white solid Compound II with a yield of 96.1% and a purity of 96.6%. 1H-NMR (400MHz, DMSO-d6): 4.34 (s, 1H), 2.08 (m, 2H), 1.46-1.24 (m, 12H), 7.73 (s, 1H), 13.24 (s, 1H); m / z(ESI + )224.0(MH) + .

Embodiment 2

[0039] Synthesis of Compound II

[0040] Glyoxylic acid monohydrate 22.1g (0.24mol, 1.2eq), 3-amino-1-adamantanol 33.5g (0.20mol, 1.0eq), triethylamine 20.2g (0.20mol, 1.0eq) and 250g di Chloromethane was put into the reaction flask, 40.9g (0.40mol, 2.0eq) of acetic anhydride was added dropwise, stirred at room temperature for 10 hours, and the remaining raw materials were controlled by HPLC to less than 3%, 50g of water was added, stirred for 30 minutes, separated, and the water layer was used 50g of dichloromethane was extracted once, and the organic layer was concentrated under reduced pressure to obtain 41.8g of off-white solid compound II, with a yield of 93.7% and a purity of 94.2%; m / z (ESI + )224.0(MH) + .

Embodiment 3

[0042] Synthesis of Compound III

[0043]Under nitrogen protection, compound II 42.8g (0.19mol, 1.0eq), (S)-pyrrolidine-2-carbonitrile 18.3g (0.19mol, 1.0eq), boric acid tris(2,2, Put 11.7g (38mmol, 0.2eq) of 2-trifluoroethyl) ester and 350g toluene into the reaction flask connected with the water separator, heat and reflux for 12 hours, separate 3.4g of water, crystallize at room temperature, filter, filter 50.5g of white solid compound III was obtained, with a yield of 88.2% and a purity of 98.6%. 1 H-NMR(400MHz, CDCl3):1.45-1.64(m,14H),2.09(m,1H),2.25-2.38(m,4H),3.40-3.54(m,1H),3.57-3.67(m,1H ),4.70-4.75(t,1H),7.79(s,1H).m / z(ESI + )302.2 (MH) + .

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a synthesizing method of vildagliptin, and belongs to the field of medicine intermediate synthesis. The method includes the steps of conducting an imidization with 3-amino-1-adamantanol and monohydrated glyoxylic acid as the raw materials to obtain (3-hydroxyl adamantly imino)acetic acid, conducting acylation condensation on the (3-hydroxyl adamantly imino)acetic acid and (S)-pyrrolidine-2-formonitrile under the catalysis of electron-withdrawing phenylboric acid to obtain (2S)-1-[[(3-hydroxyl tricyclic[3,3,1,1[3,7]]decane-1-yl)imino]acetyl]pyrrolidine-2-formonitrile, and then conducting hydrazine hydrate reduction to obtain vildagliptin. A one-pot method is adopted, operation is simple, impurities are few, the product is easy to purify, the purifying steps are reduced, cost is reduced, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for synthesizing vildagliptin. Background technique [0002] Vildagliptin chemical name (-)-(2S)-1-[[(3-hydroxytricyclo[3.3.1.1[3,7]]decane-1-yl)amino]acetyl]pyrrolidine-2 -formonitrile (structure shown in formula (I)), vildagliptin is a dipeptidylase type IV (DDPIV) inhibitor developed by Novartis, Switzerland, which can be used to treat type 2 diabetes, either alone or Combined use with other antidiabetic drugs can significantly reduce the level of glycosylated hemoglobin, has good tolerance and no significant adverse reactions, and is a new diabetes drug with good application prospects. In September 2007, it was approved as a low-dose drug by the European Union, and it has also been approved in Brazil and Mexico. [0003] [0004] There are many synthetic methods of vildagliptin reported in the literature, mainly including the following methods: [0005...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D207/16
CPCC07D207/16
Inventor 蒋道来高峰谢楠
Owner 无锡科华生物科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com